Skip to main content

The influence of uterine leiomyomatosis on the onset of psoriasis: a nationwide population-based study of 2.5 million Korean females

Abstract

Background

Uterine leiomyomatosis and psoriasis are prevalent conditions and shared pathophysiological factors indicate a potential association. However, a direct correlation has not been established. We investigated the relationship between uterine leiomyomatosis and the risk of new-onset psoriasis in Korean females of reproductive age.

Methods

This nationwide population-based study used data from the Korean National Health Insurance System database. Data from 2,755,790 Korean females 20–39 years of age who underwent health check-ups from 2009 to 2012 were analyzed. Monitoring began at the initial national health assessment within the time frame and continued until either the diagnosis of emerging psoriasis or until December 2018.

Results

Among 2,503,769 females included, 1.96% were diagnosed with psoriasis and 0.72% with uterine leiomyomatosis. The incidence ratio for new-onset psoriasis was higher in uterine leiomyomatosis patients (3.13 per 1,000) than in subjects without uterine leiomyomatosis (2.72 per 1,000). The hazard ratio for psoriasis occurrence was 1.18 (1.07–1.31) in uterine leiomyomatosis patients, 1.22 (1.08–1.37) in subjects who did not undergo myomectomy, and 1.12 (0.94–1.33) in patients who underwent myomectomy.

Conclusions

Uterine leiomyomatosis patients, especially those not undergoing myomectomy, showed an increased risk of psoriasis. Lifestyle modifications and surgical intervention for uterine leiomyomatosis may also be beneficial for psoriasis occurrence.

Peer Review reports

Introduction

Uterine leiomyomatosis (uterine fibroid or uterine myoma) is the predominant benign uterine tumor found in females of reproductive age [1]. This condition is characterized by the presence of a fibroid pseudocapsule, a complex fibro-neurovascular structure that delineates the uterine leiomyomatosis from the adjacent normal peripheral myometrium [2, 3]. Uterine leiomyomatosis can vary in size, number, and location depending on the individual [2, 4]. The incidence of uterine leiomyomatosis widely varies across studies and geographical regions (4.5–68.6%) and this variation can be attributed to differences in the nature of the investigation, the diagnostic techniques used, and the racial or ethnic composition of the populations studied [5, 6]. Although a benign tumor, uterine leiomyomatosis can become an indication for hysterectomy in some cases, and can cause menorrhagia, pelvic pain, infertility, recurrent miscarriage, and preterm labor [2, 7, 8]. Although uterine leiomyomatosis is typically benign, misdiagnosis of uterine leiomyosarcoma, a rare but aggressive malignancy, can occur due to overlapping symptoms such as abnormal bleeding and pelvic masses [9]​. Accurate differentiation is critical as leiomyosarcomas require more invasive treatments like hysterectomy, while leiomyomas may be managed conservatively [9]. Raffone et al. (2023) reported that ultrasound alone has moderate diagnostic accuracy, with 76% sensitivity and 89% specificity, emphasizing the need for a more comprehensive diagnostic approach, including imaging and biopsy, to avoid inappropriate treatments [9]​.

The pathophysiology of uterine leiomyomatosis involves the transformation of smooth muscle stem cells (myometrial stem cells) within the myometrium [7, 10]. This transformation occurs through the paracrine mechanisms mediated by estrogen, progesterone, and WNT/β-catenin pathway, forming fibroid progenitor cells [7, 11]. In addition, various growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF) [12], exert effects on the myometrium and leiomyoma, contributing to the pathophysiology of uterine leiomyomatosis. Risk factors for uterine leiomyomatosis include older age, race, nulliparity, premenopause, family history of uterine leiomyomatosis, hypertension (HTN), food additives, soy milk, obesity, low vitamin D levels, high vitamin E levels, microbiome change, endocrine-disrupting chemicals, smoking, and alcohol consumption [2, 13,14,15,16,17,18,19,20,21,22,23,24,25].

Psoriasis is a chronic inflammatory skin disease that appears primarily as well-demarcated, erythematous scaly plaques predominantly manifesting in symmetrical patterns on elbows, knees, trunk, and scalp [26,27,28]. Globally, the prevalence rate is approximately 2%, with reported cases of over 60 million adults and children affected [29,30,31,32]. Psoriasis is triggered by the activation of plasmacytoid dendritic cells due to genetic and environmental factors, leading to the production of various proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-22, IL-23, and IL-1β [33], resulting in chronic inflammation through excessive keratinocyte proliferation [26, 34]. The risk factors for psoriasis include mechanical stress, smoking, alcohol consumption, air pollution, metabolic syndrome, obesity, HTN, diabetes mellitus (DM), dyslipidemia, drugs, vaccination, infection, and mental stress [27, 29].

Although direct correlations between uterine leiomyomatosis and psoriasis have not been reported to date, emerging evidence indicates a potential association [35,36,37]. Therefore, in the present study, the association between uterine leiomyomatosis and the likelihood of developing new-onset psoriasis among Korean females of reproductive age was investigated utilizing a comprehensive national health screening cohort.

Methods

Study design and database

This retrospective cohort study utilized the Korean National Health Insurance System (K-NHIS) to analyze data from a population-based cohort. Data were collected from the K-NHIS that contains invoicing records of healthcare professionals and includes details on patient age, gender, demographic features, past treatments, overall health evaluations, lifestyle, and habits. Medical professionals are recommended to perform regular medical checks either every 2 years or annually. Korea has more than 50 million residents and subscribing to the K-NHIS is mandatory for all citizens [38,39,40].

Study population

Data from 2,755,790 Korean females 20–39 years of age who underwent health check-ups from 2009 to 2012 were analyzed. The 20–39 age range was selected as it represents the primary reproductive age group for women and has a high incidence of uterine leiomyomatosis. Inclusion criteria involved females diagnosed with uterine leiomyomatosis within the designated period, with no prior history of psoriasis. Uterine leiomyomatosis was defined based on the International Classification of Diseases, Tenth Revision (ICD-10) code D25 in the K-NHIS database [41], while psoriasis was defined by the ICD-10 code L40 [42]. A diagnosis of psoriasis was confirmed by having either two outpatient records or a single inpatient record with these codes within a year. Participants who underwent hysterectomy during the analysis period, were previously diagnosed with psoriasis during screening period (from January 2002 to their initial health check-up), were diagnosed with psoriasis within 1 year of the starting examination to account for a latency period, or had incomplete data on uterine leiomyomatosis were excluded. Monitoring for the development of psoriasis began at the initial national health assessment within the time frame and continued until either the diagnosis of emerging psoriasis or until December 2018. Consequently, the present study included 2,503,769 females 20–39 years of age. The flowchart depicting the inclusion process for the study population is shown in Fig. 1. Due to the retrospective nature of the study and the reliance on anonymous databases and publicly available medical records, the Institutional Review Board at Seoul St. Mary’s Hospital, Catholic University of Korea approved the study (KC22ZISI0317).

Fig. 1
figure 1

Study flow chart

Measurements and definitions

Body mass index (BMI) was determined by dividing patient weight in kilograms by the square of height in meters (kg/m2). A BMI ≥ 25 kg/m2 was defined as obesity [43, 44] . Household income was divided into two categories: income in the bottom quartile based on monthly contributions to the National Health Insurance Corporation and the remainder [44, 45].

The initial comorbid conditions of the study population were identified using the ICD-10 classification codes. The following ICD-10 codes were used: uterine leiomyomatosis (D25), DM (E10–E14), HTN (I10–I15), dyslipidemia (E78), stroke (I63, I64), and ischemic heart ailments (I20–I25). For DM, the criteria were either a minimum of one yearly claim under ICD-10 codes E10–E14 and one yearly claim for antidiabetic medicine prescription, or a fasting blood sugar level ≥ 126 mg/dL. HTN was defined as either a minimum of one yearly claim under ICD-10 codes I10–I15 and one yearly claim for antihypertensive drug prescription, or a blood pressure measurement ≥ 140/90 mm Hg. Dyslipidemia was defined as either at least one yearly claim under ICD-10 code E78 and one yearly claim for cholesterol-lowering drug prescription, or an overall cholesterol measure ≥ 240 mg/dL. Any other health complications were noted if one or multiple diagnostic entries were available.

Social behaviors including smoking habits, alcohol intake, and physical exertion, were determined using personal disclosure questionnaires. For smoking habits, classification included current smoker, ex-smoker, or never-smoker based on responses. A current smoker was considered a person currently smoking and who had consumed > 5 packs or a cumulative of 100 cigarettes in their lifetime. An ex-smoker was considered a subject who previously consumed > 5 packs but had since quit by the time of the questionnaire. Never-smokers were individuals who had consumed ≤ 5 packs [44, 46]. Regarding alcohol intake, individuals consuming ≥ 30 g daily were considered heavy drinkers and subjects consuming < 30 g daily were mild to moderate drinkers. Individuals participating in intense physical exercise for over 20 min at least three times a week, or moderate exercise for over 30 min at a minimum of five times a week, were considered to participate in regular physical activity.

Study outcomes and follow-up

In the present study, a psoriasis diagnosis was confirmed by having either two outpatient records or a single inpatient record under the ICD-10 code for psoriasis (L40) in the K-NHIS database within 1 year following the index examination. The primary endpoint of the investigation was to identify the emergence of new-onset psoriasis cases. The incidence rate of new-onset psoriasis was determined as the count of new cases per 1,000 patient-years of follow-up. Furthermore, how uterine leiomyomatosis influences the onset of psoriasis was investigated.

Statistical analysis

Numerical data are represented as the mean ± standard deviation (SD) and/or as the geometric mean within a 95% confidence interval (CI). Countable data are depicted through counts and their corresponding percentages. The Student’s t-test was used to assess differences in continuous variables and the chi-square test for categorical variables. We used Cox proportional hazards models to calculate hazard ratios (HR) for the development of psoriasis, which accounts for the time-to-event nature of the data and allows for varying follow-up times among participants, estimating the HR and its 95% CI for each independent factor. Model 1 remained unadjusted and the multifactorial regression Model 2 factored in age, smoking status, alcohol consumption, and consistent physical activity. Model 3 incorporated all components of Model 2 along with DM, HTN, dyslipidemia, chronic kidney disease (CKD), and BMI. The Kaplan-Meier method was used for the HRs for uterine leiomyomatosis, considering both surgical and no surgical interventions. All statistical calculations were conducted using the SAS software (version 9.4; SAS Institute Inc., Cary, NC, USA) with P-values ≤ 0.05 indicative of statistical significance.

Results

Baseline characteristics of the study population

Among the 2,503,769 females included in the analysis, 49,177 (1.96%) were diagnosed with psoriasis during the study period, 18,025 (0.72%) were diagnosed with uterine leiomyomatosis, and 5,854 (0.23%) underwent myomectomy.

The baseline characteristics of the study population are summarized in Table 1. Among individuals 20–29 years of age, 26,511 (2.04%) were diagnosed with psoriasis compared with 22,666 (1.89%) subjects 30–39 years of age. Furthermore, a higher incidence of psoriasis was observed in cases with a medical history of coexisting conditions such as uterine leiomyomatosis (406 cases, 2.25%), DM (557 cases, 2.37%), HTN (1,238 cases, 2.11%), dyslipidemia (1,999 cases, 2.15%), and CKD (1,571 cases, 2.28%). The incidence of psoriasis was increased in individuals who smoked (3,490 cases, 2.35% in current smokers) and consumed alcohol (1,355 cases, 2.27% in heavy drinkers). Conversely, subjects in the lowest 25% income bracket exhibited a lower incidence of psoriasis (10,393 cases, 1.91%).

Table 1 Baseline characteristics of subjects

Incidence and association of psoriasis with uterine leiomyomatosis and myomectomy status

In subjects without uterine leiomyomatosis, the incidence ratio for new-onset psoriasis was 2.72 per 1,000 individuals (48,771 cases out of 2,485,744 individuals), and among uterine leiomyomatosis patients, this ratio was higher at 3.13 per 1,000 individuals (406 cases out of 18,025 individuals). In multivariate analysis, after adjusting for age, smoking status, alcohol consumption, regular physical activity, DM, HTN, dyslipidemia, CKD, and BMI, the HR for psoriasis occurrence was 1.18 (95% CI: 1.07–1.31) in uterine leiomyomatosis patients (Table 2, Model 3). The HR was 1.22 (95% CI: 1.08–1.37) in the uterine leiomyomatosis patients who did not undergo myomectomy (281 cases out of 12,717 individuals), and 1.12 (95% CI: 0.94–1.33) in the uterine leiomyomatosis patients who did undergo myomectomy (125 cases out of 5,854 individuals) (Table 3, Model 3).

Table 2 Risk of new-onset psoriasis associated with uterine leiomyomatosis
Table 3 Risk of new-onset psoriasis based on uterine leiomyomatosis and myomectomy status

In the Kaplan-Meier survival assessment where the outcome was a diagnosis of psoriasis, the uterine leiomyomatosis patients who did not undergo myomectomy had the lowest rate of disease-free survival, with a cumulative incidence of psoriasis of approximately 3.5% at 10 years follow-up, compared to approximately 3% for those who underwent myomectomy and 2.5% for those without uterine leiomyomatosis (Fig. 2).

Fig. 2
figure 2

Kaplan-Meier curves of psoriasis incidence by uterine leiomyomatosis (a) and myomectomy status (b)

Discussion

In the present study, results showed an increased risk of psoriasis in patients with uterine leiomyomatosis, and a more increased risk of psoriasis in patients with uterine leiomyomatosis who did not undergo myomectomy. A potential association between these conditions exists due to shared risk factors such as HTN, obesity, smoking, and alcohol consumption.

Studies examining the association between uterine leiomyomatosis and immune system-related diseases are relatively scarce [35]. The relationship with systemic lupus erythematosus (SLE) remains unclear, with one small study showing a lower SLE prevalence in women with uterine fibroids compared to those with endometriosis [36]. However, women with endometriosis have an increased risk of developing uterine fibroids [37], suggesting a complex interrelationship. Research on thyroid disorders shows mixed results, with some studies indicating an increased risk of autoimmune thyroid disorders in women with endometriosis [35, 47]. Similarly, the association with rheumatoid arthritis (RA) is inconsistent, with some studies reporting an increased risk [48] and others finding no significant association [49]. A large case-control study found a significantly increased risk of inflammatory bowel disease (IBD) in pregnant women with a history of endometriosis (OR = 2.06, 95% CI: 1.83–2.31) [50]. Similarly, a cohort study reported an increased incidence of IBD in women with endometriosis (SIR = 1.5, 95% CI: 1.4–1.7) [51]. However, these studies primarily focused on endometriosis rather than uterine leiomyomatosis specifically [35]. Overall, the quality of evidence for these associations is generally low, and further large-scale, well-designed studies are needed to clarify the relationship between uterine leiomyomatosis and immune system-related diseases [35].

Furthermore, the pathophysiology of uterine leiomyomatosis and psoriasis could be associated through common pathways such as WNT/β-catenin, TNF-α, VEGF, and bFGF.

In the pathophysiology of uterine leiomyomatosis, the transformation of smooth muscle stem cells occurs through paracrine mechanisms mediated by the WNT/β-catenin pathway. The increased growth observed in fibroids with mutations in the mediator complex subunit 12 (MED12) may be explained by the interaction between estrogen and the WNT/β-catenin pathway, combined with TGF-β [7]. Furthermore, mutations in MED12 have been identified in rare fibroid variations, including atypical, cellular, and lipoleiomyomas in addition to leiomyosarcomas and smooth muscle tumors with uncertain malignant potential [7, 52]. TNF-α is a cytokine secreted from activated macrophages and plays a role in regulating inflammation, immunity, cell growth and differentiation, and apoptosis. The TNF-α protein expression was higher in uterine leiomyomatosis compared with normal myometrial tissue [53,54,55]. In addition, a more pronounced VEGF expression was observed in leiomyomas compared with the adjacent myometrium indicating that local angiogenesis might play a pivotal role in the tumorigenesis and growth of these tumors [56]. Furthermore, the expression of bFGF and its receptors, fibroblast growth factor receptor (FGFR)-1 and FGFR-2, was found in both leiomyomas and myometrial cells in previous studies [12, 58,58,59,60,61,62]. Notably, a more pronounced FGFR-1 expression was observed in the tumors compared with the myometrium [62].

Evidence has been provided in multiple investigations for the involvement of the WNT/β-catenin pathway and TNF-α in the pathophysiology of psoriasis. In a previous study, psoriasis lesions were investigated through biopsy and examining WNT molecules of the WNT/β -catenin pathway and the authors determined that Wnt5a levels were elevated 4-fold in the lesional skin [63]. In another study in which Wnt5a was investigated, knockdown of Wnt5a in cultured HaCaT keratinocytes and normal human keratinocytes suppressed keratinocyte proliferation and induced apoptosis [64]. TNF-α is notably upregulated in the keratinocytes present in psoriatic lesions [65]. TNF-α, produced by mast cells, macrophages, keratinocytes, and lymphocytes, apparently increases the expression of IL-8, VEGF, bFGF, angiopoietin, and Tie-2 (angiopoietin receptor) receptor in endothelial cells [66, 67]. Patients with psoriasis exhibit elevated serum VEGF levels, and a notable correlation exists between the severity of psoriasis and these VEGF levels [68,69,70]. Furthermore, the increased VEGF expression in skin samples from individuals with psoriasis [71] emphasizes its pivotal role in preserving the integrity of the epidermal barrier [72]. This connection between epidermal VEGF and keratinocyte proliferation indicates a significant involvement of VEGF in the proliferation of keratinocytes [72,73,74].

Notably, among individuals with uterine leiomyomatosis, the patients that underwent myomectomy did not exhibit a significant increase in the HR for the occurrence of psoriasis. In contrast, the patients that did not undergo myomectomy showed a statistically significant increase in HR for psoriasis development. These results are due to the changes in cytokines that occur after myomectomy. In a recent study, TNF-α levels decreased in patients with uterine intramural leiomyoma following myomectomy as evidenced by endometrial sampling [75]. In another study in which the treatment of uterine leiomyomatosis was investigated using mifepristone and ultrasound-guided radiofrequency ablation, the authors observed a significant reduction in the serum levels of VEGF, epidermal growth factor (EGF), bFGF, TGF-β, and TGF-β receptor among patients after either ultrasound-guided radiofrequency ablation or the combined approach of oral administration of mifepristone with ultrasound-guided radiofrequency ablation [76]. Changes in these cytokines can occur even after myomectomy, and consequently, may influence the onset of psoriasis.

The present study had several limitations. In the process of including the research population, individuals who underwent hysterectomy during the study period were excluded. However, in the situation of uterine leiomyomatosis patients experiencing heavy menstrual bleeding and no longer desiring pregnancy, hysterectomy might have been performed [7]. Consequently, a potential exists for the exclusion of such patients from the study. Furthermore, because the data were based on medical records of patient hospital visits, a bias arising from the absence of records may exist for individuals with diseases such as uterine leiomyomatosis or psoriasis if they did not seek medical treatment. Our study is limited by the lack of histological confirmation in defining uterine leiomyomatosis, relying instead on ICD-10 codes from medical records. Additionally, the specific diagnostic methods used (e.g., ultrasound, magnetic resonance imaging) are not available in this database, which further limits the precision of the diagnosis. This approach, while enabling a large-scale population study, may have led to some misclassification of cases. We were unable to adjust for potential confounding factors such as medication use (e.g., propranolol) or certain medical conditions (e.g., hyperthyroidism) that may influence psoriasis development. Future studies should aim to include these variables in their analyses. Another limitation of this study is that we did not account for the potential delayed diagnosis of uterine leiomyomatosis. Our study design, which used a fixed baseline period for leiomyomatosis diagnosis, may have missed cases diagnosed later in the follow-up period. Future studies should consider time-varying exposure analyses to address this potential bias and capture diagnoses of leiomyomatosis that occur throughout the study period. Additionally, future studies should extend this analysis to women aged 40–59 and consider stratification by menopausal status to provide a more comprehensive understanding of the association between uterine leiomyomatosis and psoriasis across different age groups and hormonal states. However, considering the age of onset of psoriasis, it was thought that focusing on subsequent psoriasis in individuals with leiomyomatosis aged 20–39 could yield more worthy results.

Despite the limitations, the present study had several strengths. The results provide significant contributions. A comprehensive national database representative of all Korean women of reproductive age was used to explore the relationship between uterine leiomyomatosis and psoriasis. To the best of our knowledge, this is the first research in which the association between uterine leiomyomatosis and the likelihood of developing psoriasis was investigated. Furthermore, by comparing the HR of psoriasis based on the myomectomy status, the importance of surgical treatment for uterine leiomyomatosis was substantiated. From a clinical perspective, practitioners should be aware of the potential association between these conditions. When treating patients with psoriasis, especially women of reproductive age, clinicians might consider screening for uterine leiomyomatosis. Conversely, women diagnosed with leiomyomatosis should be informed about the slightly increased risk of developing psoriasis and advised to report any skin changes promptly.

Conclusions

In conclusion, among female patients with uterine leiomyomatosis, the risk of developing psoriasis was higher compared with subjects without uterine leiomyomatosis. Furthermore, the risk of psoriasis was greater in leiomyoma patients without myomectomy. Therefore, adopting lifestyle modifications (e.g., quitting smoking and drinking alcohol) and preventing accompanying conditions such as HTN, diabetes, and hyperlipidemia, is important. In addition, performing myomectomy for uterine leiomyomatosis may be beneficial for psoriasis occurrence; however, additional studies are needed to elucidate the underlying processes.

Data availability

Availability of data and materialsThe datasets analysed during the current study are available from the NHIS data sharing service data (https://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do).

Abbreviations

BMI:

Body mass index

bFGF:

Basic fibroblast growth factor

CI:

Confidence interval

CKD:

Chronic kidney disease

DM:

Diabetes mellitus

EGF:

Epidermal growth factor

FGFR:

Fibroblast growth factor receptor

HR:

Hazard ratio

HTN:

Hypertension

ICD:

10-International classification of diseases, tenth revision

IFN:

Interferon

IGF:

Insulin-like growth factor

IL:

Interleukin

K:

NHIS-Korean national health insurance system

MED12:

Mediator complex subunit 12

SD:

Standard deviation

TGF:

β-Transforming growth factor beta

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

References

  1. Ciebiera M, Wlodarczyk M, Zgliczynski S, Lozinski T, Walczak K, Czekierdowski A. The role of miRNA and related pathways in pathophysiology of uterine fibroids-from bench to Bedside. Int J Mol Sci. 2020;21(8):3016.

  2. Yang Q, Ciebiera M, Bariani MV, Ali M, Elkafas H, Boyer TG, Al-Hendy A. Comprehensive Review of Uterine fibroids: Developmental Origin, Pathogenesis, and treatment. Endocr Rev. 2022;43(4):678–719.

    Article  PubMed  Google Scholar 

  3. Tinelli A, Favilli A, Lasmar RB, Mazzon I, Gerli S, Xue X, Malvasi A. The importance of pseudocapsule preservation during hysteroscopic myomectomy. Eur J Obstet Gynecol Reprod Biol. 2019;243:179–84.

    Article  PubMed  Google Scholar 

  4. Jayes FL, Liu B, Feng L, Aviles-Espinoza N, Leikin S, Leppert PC. Evidence of biomechanical and collagen heterogeneity in uterine fibroids. PLoS ONE. 2019;14(4):e0215646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Giuliani E, As-Sanie S, Marsh EE. Epidemiology and management of uterine fibroids. Int J Gynaecol Obstet. 2020;149(1):3–9.

    Article  PubMed  Google Scholar 

  6. Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017;124(10):1501–12.

    Article  CAS  PubMed  Google Scholar 

  7. Stewart EA, Laughlin-Tommaso SK, Catherino WH, Lalitkumar S, Gupta D, Vollenhoven B. Uterine fibroids. Nat Rev Dis Primers. 2016;2:16043.

    Article  PubMed  Google Scholar 

  8. Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005;308(5728):1589–92.

    Article  CAS  PubMed  Google Scholar 

  9. Raffone A, Raimondo D, Neola D, Travaglino A, Raspollini A, Giorgi M, Santoro A, De Meis L, Zannoni GF, Seracchioli R, et al. Diagnostic accuracy of Ultrasound in the diagnosis of Uterine Leiomyomas and Sarcomas. J Minim Invasive Gynecol. 2024;31(1):28–e3621.

    Article  PubMed  Google Scholar 

  10. Bulun SE. Uterine fibroids. N Engl J Med. 2013;369(14):1344–55.

    Article  CAS  PubMed  Google Scholar 

  11. Ono M, Yin P, Navarro A, Moravek MB, Coon JSt, Druschitz SA, Serna VA, Qiang W, Brooks DC, Malpani SS, et al. Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci U S A. 2013;110(42):17053–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F, Vale W, Castellucci M. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update. 2011;17(6):772–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ciebiera M, Wlodarczyk M, Slabuszewska-Jozwiak A, Nowicka G, Jakiel G. Influence of vitamin D and transforming growth factor beta3 serum concentrations, obesity, and family history on the risk for uterine fibroids. Fertil Steril. 2016;106(7):1787–92.

    Article  CAS  PubMed  Google Scholar 

  14. Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol. 2001;153(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  15. Wise LA, Palmer JR, Spiegelman D, Harlow BL, Stewart EA, Adams-Campbell LL, Rosenberg L. Influence of body size and body fat distribution on risk of uterine leiomyomata in U.S. black women. Epidemiology. 2005;16(3):346–54.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ciebiera M, Wlodarczyk M, Ciebiera M, Zareba K, Lukaszuk K, Jakiel G. Vitamin D and uterine fibroids-review of the literature and novel concepts. Int J Mol Sci. 2018;19(7):2051.

  17. Sabry M, Halder SK, Allah AS, Roshdy E, Rajaratnam V, Al-Hendy A. Serum vitamin D3 level inversely correlates with uterine fibroid volume in different ethnic groups: a cross-sectional observational study. Int J Womens Health. 2013;5:93–100.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Mohammadi R, Tabrizi R, Hessami K, Ashari H, Nowrouzi-Sohrabi P, Hosseini-Bensenjan M, Asadi N. Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2020;18(1):85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ciebiera M, Szymanska-Majchrzak J, Sentkowska A, Kilian K, Rogulski Z, Nowicka G, et al. Alpha-tocopherol serum levels are increased in caucasian women with uterine fibroids: A Pilot Study. Biomed Res Int. 2018:6793726.

  20. Baker JM, Chase DM, Herbst-Kralovetz MM. Uterine microbiota: residents, tourists, or invaders? Front Immunol. 2018;9:208.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee G, Kim S, Bastiaensen M, Malarvannan G, Poma G, Caballero Casero N, Gys C, Covaci A, Lee S, Lim JE, et al. Exposure to organophosphate esters, phthalates, and alternative plasticizers in association with uterine fibroids. Environ Res. 2020;189:109874.

    Article  CAS  PubMed  Google Scholar 

  22. Bariani MV, Rangaswamy R, Siblini H, Yang Q, Al-Hendy A, Zota AR. The role of endocrine-disrupting chemicals in uterine fibroid pathogenesis. Curr Opin Endocrinol Diabetes Obes. 2020;27(6):380–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang Q, Ali M, El Andaloussi A, Al-Hendy A. The emerging spectrum of early life exposure-related inflammation and epigenetic therapy. Cancer Stud Mol Med. 2018;4(1):13–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wong JY, Chang PY, Gold EB, Johnson WO, Lee JS. Environmental tobacco smoke and risk of late-diagnosis incident fibroids in the study of women’s Health across the Nation (SWAN). Fertil Steril. 2016;106(5):1157–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Takala H, Yang Q, El Razek AMA, Ali M, Al-Hendy A. Alcohol consumption and risk of uterine fibroids. Curr Mol Med. 2020;20(4):247–58.

    Article  CAS  PubMed  Google Scholar 

  26. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol. 2020;182(4):840–8.

    Article  CAS  PubMed  Google Scholar 

  27. Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M. Risk factors for the development of Psoriasis. Int J Mol Sci. 2019;20(18):4347.

  28. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263–71.

    Article  CAS  PubMed  Google Scholar 

  29. Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker J. Psoriasis. Lancet. 2021;397(10281):1301–15.

    Article  CAS  PubMed  Google Scholar 

  30. Petit RG, Cano A, Ortiz A, Espina M, Prat J, Munoz M, et al. Psoriasis: from pathogenesis to pharmacological and Nano-Technological-based therapeutics. Int J Mol Sci. 2021;22(9):4983.

  31. Michalek IM, Loring B, John SM, World Health O. Global report on psoriasis. Geneva: World Health Organization; 2016.

    Google Scholar 

  32. Samotij D, Nedoszytko B, Bartosinska J, Batycka-Baran A, Czajkowski R, Dobrucki IT, Dobrucki LW, Gorecka-Sokolowska M, Janaszak-Jasienicka A, Krasowska D, et al. Pathogenesis of psoriasis in the omic era. Part I. Epidemiology, clinical manifestation, immunological and neuroendocrine disturbances. Postepy Dermatol Alergol. 2020;37(2):135–53.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol. 2016;38(1):11–27.

    Article  CAS  PubMed  Google Scholar 

  34. Swindell WR, Johnston A, Xing X, Voorhees JJ, Elder JT, Gudjonsson JE. Modulation of epidermal transcription circuits in psoriasis: new links between inflammation and hyperproliferation. PLoS ONE. 2013;8(11):e79253.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Shigesi N, Kvaskoff M, Kirtley S, Feng Q, Fang H, Knight JC, Missmer SA, Rahmioglu N, Zondervan KT, Becker CM. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):486–503.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Smith S, Howell R, Scott L. Is endometriosis associated with systemic lupus erythematosus? Int J Fertility. 1993;38(6):343–6.

    Google Scholar 

  37. Gallagher CS, Mäkinen N, Harris HR, Rahmioglu N, Uimari O, Cook JP, Shigesi N, Ferreira T, Velez-Edwards DR, Edwards TL, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun. 2019;10(1):4857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim YH, Kim HJ, Park JW, Han KD, Park YG, Lee YB, Lee JH. Risk for Behcet’s disease gauged via high-density lipoprotein cholesterol: a nationwide population-based study in Korea. Sci Rep. 2022;12(1):12735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ko SH, Han K, Lee YH, Noh J, Park CY, Kim DJ, Jung CH, Lee KU, Ko KS. TaskForce Team for the diabetes fact sheet of the Korean diabetes A: past and current status of adult type 2 diabetes mellitus management in Korea: a National Health Insurance Service Database analysis. Diabetes Metab J. 2018;42(2):93–100.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lee YH, Han K, Ko SH, Ko KS, Lee KU, Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes A. Data analytic process of a nationwide population-based study using National Health Information Database established by National Health Insurance Service. Diabetes Metab J. 2016;40(1):79–82.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim S, Han K, Choi SY, Yang SY, Choi SH, Yim JY, Kim JJ, Kim MJ. Alcohol consumption and the risk of new-onset uterine leiomyomas: a nationwide population-based study in 2.5 million Korean women aged 20 to 39 years. Am J Obstet Gynecol. 2023;229(1):45. e41-45 e18.

    Article  Google Scholar 

  42. Go GM, Oh HJ, Han K, Kim YH, Lee HJ, Lee JH. Hormone replacement therapy and psoriasis risk: a Nationwide Population-based Cohort Study. J Korean Med Sci. 2023;38(49):e377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kim MK, Lee WY, Kang JH, Kang JH, Kim BT, Kim SM, Kim EM, Suh SH, Shin HJ, Lee KR, et al. 2014 clinical practice guidelines for overweight and obesity in Korea. Endocrinol Metab (Seoul). 2014;29(4):405–9.

    Article  PubMed  Google Scholar 

  44. Soh H, Im JP, Han K, Park S, Hong SW, Moon JM, Kang EA, Chun J, Lee HJ, Kim JS. Crohn’s disease and ulcerative colitis are associated with different lipid profile disorders: a nationwide population-based study. Aliment Pharmacol Ther. 2020;51(4):446–56.

    Article  CAS  PubMed  Google Scholar 

  45. Song SO, Jung CH, Song YD, Park CY, Kwon HS, Cha BS, Park JY, Lee KU, Ko KS, Lee BW. Background and data configuration process of a nationwide population-based study using the Korean national health insurance system. Diabetes Metab J. 2014;38(5):395–403.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Park S, Chun J, Han KD, Soh H, Kang EA, Lee HJ, Im JP, Kim JS. Dose-response relationship between cigarette smoking and risk of ulcerative colitis: a nationwide population-based study. J Gastroenterol. 2019;54(10):881–90.

    Article  PubMed  Google Scholar 

  47. Yuk JS, Park EJ, Seo YS, Kim HJ, Kwon SY, Park WI. Graves Disease is Associated with endometriosis: a 3-Year Population-based cross-sectional study. Med (Baltim). 2016;95(10):e2975.

    Article  Google Scholar 

  48. Harris HR, Costenbader KH, Mu F, Kvaskoff M, Malspeis S, Karlson EW, Missmer SA. Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the nurses’ Health Study II. Ann Rheum Dis. 2016;75(7):1279–84.

    Article  CAS  PubMed  Google Scholar 

  49. Merlino LA, Cerhan JR, Criswell LA, Mikuls TR, Saag KG. Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women. Semin Arthritis Rheum. 2003;33(2):72–82.

    Article  CAS  PubMed  Google Scholar 

  50. de Silva PS, Hansen HH, Wehberg S, Friedman S, Nørgård BM. Risk of ectopic pregnancy in Women with Inflammatory Bowel Disease: a 22-Year Nationwide Cohort Study. Clin Gastroenterol Hepatol. 2018;16(1):83–e8981.

    Article  PubMed  Google Scholar 

  51. Jess T, Frisch M, Jørgensen KT, Pedersen BV, Nielsen NM. Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study. Gut. 2012;61(9):1279–83.

    Article  PubMed  Google Scholar 

  52. Pérot G, Croce S, Ribeiro A, Lagarde P, Velasco V, Neuville A, Coindre JM, Stoeckle E, Floquet A, MacGrogan G, et al. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS ONE. 2012;7(6):e40015.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Islam MS, Ciavattini A, Petraglia F, Castellucci M, Ciarmela P. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018;24(1):59–85.

    Article  CAS  PubMed  Google Scholar 

  54. Kurachi O, Matsuo H, Samoto T, Maruo T. Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone. J Clin Endocrinol Metab. 2001;86(5):2275–80.

    CAS  PubMed  Google Scholar 

  55. Plewka A, Madej P, Plewka D, Kowalczyk A, Miskiewicz A, Wittek P, Leks T, Bilski R. Immunohistochemical localization of selected pro-inflammatory factors in uterine myomas and myometrium in women of various ages. Folia Histochem Cytobiol. 2013;51(1):73–83.

    Article  CAS  PubMed  Google Scholar 

  56. Gentry CC, Okolo SO, Fong LF, Crow JC, Maclean AB, Perrett CW. Quantification of vascular endothelial growth factor-A in leiomyomas and adjacent myometrium. Clin Sci (Lond). 2001;101(6):691–5.

    Article  CAS  PubMed  Google Scholar 

  57. Pekonen F, Nyman T, Rutanen EM. Differential expression of keratinocyte growth factor and its receptor in the human uterus. Mol Cell Endocrinol. 1993;95(1–2):43–9.

    Article  CAS  PubMed  Google Scholar 

  58. Mangrulkar RS, Ono M, Ishikawa M, Takashima S, Klagsbrun M, Nowak RA. Isolation and characterization of heparin-binding growth factors in human leiomyomas and normal myometrium. Biol Reprod. 1995;53(3):636–46.

    Article  CAS  PubMed  Google Scholar 

  59. Nowak RA. Novel therapeutic strategies for leiomyomas: targeting growth factors and their receptors. Environ Health Perspect. 2000;108(Suppl 5):849–53.

    Article  CAS  PubMed  Google Scholar 

  60. Wu X, Blanck A, Olovsson M, Moller B, Lindblom B. Expression of basic fibroblast growth factor (bFGF), FGF receptor 1 and FGF receptor 2 in uterine leiomyomas and myometrium during the menstrual cycle, after menopause and GnRHa treatment. Acta Obstet Gynecol Scand. 2001;80(6):497–504.

    CAS  PubMed  Google Scholar 

  61. Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect. 2003;111(8):1037–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wolanska M, Bankowski E. Fibroblast growth factors (FGF) in human myometrium and uterine leiomyomas in various stages of tumour growth. Biochimie. 2006;88(2):141–6.

    Article  CAS  PubMed  Google Scholar 

  63. Reischl J, Schwenke S, Beekman JM, Mrowietz U, Sturzebecher S, Heubach JF. Increased expression of Wnt5a in psoriatic plaques. J Invest Dermatol. 2007;127(1):163–9.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang Y, Tu C, Zhang D, Zheng Y, Peng Z, Feng Y, Xiao S, Li Z. Wnt/beta-Catenin and Wnt5a/Ca pathways regulate proliferation and apoptosis of keratinocytes in Psoriasis lesions. Cell Physiol Biochem. 2015;36(5):1890–902.

    Article  CAS  PubMed  Google Scholar 

  65. Heidenreich R, Rocken M, Ghoreschi K. Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol. 2009;90(3):232–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Scott BB, Zaratin PF, Colombo A, Hansbury MJ, Winkler JD, Jackson JR. Constitutive expression of angiopoietin-1 and – 2 and modulation of their expression by inflammatory cytokines in rheumatoid arthritis synovial fibroblasts. J Rheumatol. 2002;29(2):230–9.

    CAS  PubMed  Google Scholar 

  67. Lee HJ, Hong YJ, Kim M. Angiogenesis in chronic inflammatory skin disorders. Int J Mol Sci. 2021;22(21):12035

  68. Bhushan M, McLaughlin B, Weiss JB, Griffiths CE. Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis. Br J Dermatol. 1999;141(6):1054–60.

    Article  CAS  PubMed  Google Scholar 

  69. Nielsen HJ, Christensen IJ, Svendsen MN, Hansen U, Werther K, Brunner N, Petersen LJ, Kristensen JK. Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis. Inflamm Res. 2002;51(11):563–7.

    Article  CAS  PubMed  Google Scholar 

  70. Nofal A, Al-Makhzangy I, Attwa E, Nassar A, Abdalmoati A. Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control. J Eur Acad Dermatol Venereol. 2009;23(7):803–6.

    Article  CAS  PubMed  Google Scholar 

  71. Armstrong AW, Voyles SV, Armstrong EJ, Fuller EN, Rutledge JC. Angiogenesis and oxidative stress: common mechanisms linking psoriasis with atherosclerosis. J Dermatol Sci. 2011;63(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  72. Elias PM, Arbiser J, Brown BE, Rossiter H, Man MQ, Cerimele F, Crumrine D, Gunathilake R, Choi EH, Uchida Y, et al. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis. Am J Pathol. 2008;173(3):689–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Man XY, Yang XH, Cai SQ, Yao YG, Zheng M. Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol Med. 2006;12(7–8):127–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Marina ME, Roman II, Constantin AM, Mihu CM, Tataru AD. VEGF involvement in psoriasis. Clujul Med. 2015;88(3):247–52.

    PubMed  PubMed Central  Google Scholar 

  75. Kali Z, Cagiran FT. Surgical removal of intramural fibroids improves the TNF-α induced inflammatory events in endometrium. Eur Rev Med Pharmacol Sci. 2022;26(24):9180–6.

    CAS  PubMed  Google Scholar 

  76. Hou A, Yan Z, Zhang Y, Hou J, Tan S. Oral Administration of Mifepristone Combined with ultrasound-guided Radiofrequency ablation in treating patients with uterine fibroids: efficacy, Safety, and alternations of Inflammatory cytokines, Adhesion molecules, and growth factors. J Nanomaterials. 2021;2021:1–7.

    Article  Google Scholar 

Download references

Acknowledgements

None.

Funding

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2018R1D1A1B07044100).

Author information

Authors and Affiliations

Authors

Contributions

Y.H.K., H.J.K. and J.H.L. were responsible for the conception and design of the study. K.D.H. was responsible for acquisition of data. Y.H.K., H.J.K., J.Y.D., K.D.H. and J.H.L. performed the data analysis. Y.H.K. and H.J.K. drafted the manuscript. J.H.L. contributed on revising the manuscript content. All authors participated in interpretation of the findings and all authors read and approved the final version of the manuscript. Y.H.K. and H.J.K. contributed equally to the work as first authors.

Corresponding author

Correspondence to Ji Hyun Lee.

Ethics declarations

Ethics approval and consent to participate

The study was performed in accordance with the ethical standards of the Declaration of Helsinki (1964) and its subsequent amendments. All data from the NHIS of Korea were collected with written informed consent from all participants. Data in this study was anonymized prior to the release of authors from the NHIS. This study was approved by the Institute Review Board (IRB) of the Seoul St. Mary’s Hospital (IRB number: KC22ZISI0317).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, Y.H., Kim, H.J., Doh, J.Y. et al. The influence of uterine leiomyomatosis on the onset of psoriasis: a nationwide population-based study of 2.5 million Korean females. BMC Women's Health 25, 50 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12905-024-03529-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12905-024-03529-7

Keywords